Structure of a BCOR Corepressor Peptide in Complex with the BCL6 BTB Domain Dimer

Ghetu, Alexandru F.; Corcoran, Connie M.; Cerchietti, Leandro; Bardwell, Vivian J.; Melnick, Ari; Privé, Gilbert G.

doi:10.1016/j.molcel.2007.12.026

Cited by 153 publications

(228 citation statements)

References 24 publications

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“…Transcription factors with a BTB domain at the N-terminus comprise a large important class of molecules involved in development and carcinogenesis. As shown in crystallographic studies, the BTB domains from PLZF (promyelocytic leukemia zinc finger), 2,3 BCL6, 4,5 LRF/ZBTB7, 6,7 Bach1, 8 and FAZF 9 are tightly interwound homodimers. In the case of Miz1, there are contradicting crystallographic data that BTB exists as either homodimer 9 or homotetramer.…”

Section: Introductionmentioning

confidence: 89%

Drosophila BTB/POZ Domains of “ttk Group” Can Form Multimers and Selectively Interact with Each Other

Bonchuk

Denisov

Georgiev

et al. 2011

Journal of Molecular Biology

105

109

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Edited by M. GottesmanKeywords: GAGA; BTB domain; Mod(mdg4); CP190; chromatin insulatorThe BTB (bric-a-brac, tramtrack and broad complex)/POZ (poxvirus and zinc finger) domain is a conserved protein-protein interaction motif contained in a variety of transcription factors involved in development, chromatin remodeling, insulator activity, and carcinogenesis. All wellstudied mammalian BTB domains form obligate homodimers and, rarely, tetramers. Only the BTB domain of the Drosophila GAGA factor (GAF) has been shown to exist as higher-order multimers. The BTB domain of GAF belongs to the "ttk group" that contains several highly conserved sequences not found in other BTB domains. Here, we have shown by size-exclusion chromatography, chemical cross-linking, and nondenaturing PAGE that four additional BTB domains of the ttk group-Batman, Mod(mdg4), Pipsqueak, and Tramtrack-can form multimers, like GAF. Interestingly, the BTB domains of GAF and Batman have formed a wide range of complexes and interacted in the yeast two-hybrid assay with other BTB domains tested. In contrast, the BTB domains of Mod(mdg4), Pipsqueak, and Tramtrack have formed stable high-order multimer complexes and failed to interact with each other. The BTB domain of Drosophila CP190 protein does not belong to the ttk group. This BTB domain has formed stable dimers and has not interacted with domains of the ttk group. Previously, it was suggested that GAF oligomerization into higher-order complexes facilitates long-range activation by providing a protein bridge between an enhancer and a promoter. Unexpectedly, experiments in the Drosophila model system have not supported the role of GAF in organization of longdistance interaction between the yeast GAL4 activator and the white promoter.© 2011 Elsevier Ltd. All rights reserved. IntroductionThe BTB (bric-a-brac, tramtrack and broad complex) domain [also known as the POZ (poxvirus and zinc finger) domain] is a versatile protein-protein interaction motif that participates in a wide range of cellular functions, including transcription regulation (for review, see Ref. 1 ). Transcription factors with a BTB domain at the N-terminus comprise a large important class of molecules involved in development and carcinogenesis. As shown in crystallographic studies,

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Section: Introductionmentioning

confidence: 89%

Drosophila BTB/POZ Domains of “ttk Group” Can Form Multimers and Selectively Interact with Each Other

Bonchuk

Denisov

Georgiev

et al. 2011

Journal of Molecular Biology

105

109

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“…4,18,19 Recently, the OFCD with BCOR mutation Y Kondo et al minimal BCL-6 binding site was identified within residues 498-514, which is located in exon 4. 20 In this study, a novel BCOR mutation, c.888delG (p.N297IfsX80) in exon 4, was found in this family. We assumed the mutant transcript with this mutation may undergo nonsense-mediated mRNA decay, but we could not confirm it as no living cells were available from the patients.…”

Section: Resultsmentioning

confidence: 51%

A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS

et al. 2012

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Oculofaciocardiodental syndrome (OFCD) is an X-linked dominant disorder associated with male lethality, presenting with congenital cataract, dysmorphic face, dental abnormalities and septal heart defects. Mutations in BCOR (encoding BCL-6-interacting corepressor) cause OFCD. Here, we report on a Korean family with common features of OFCD including bilateral 2nd-3rd toe syndactyly and septal heart defects in three affected females (mother and two daughters). Through the mutation screening and copy number analysis using genomic microarray, we identified a novel heterozygous mutation, c.888delG, in the BCOR gene and two interstitial microduplications at Xp22.2-22.13 and Xp21.3 in all the three affected females. The BCOR mutation may lead to a premature stop codon (p.N297IfsX80). The duplication at Xp22.2-22.13 involved the NHS gene causative for Nance-Horan syndrome, which is an X-linked disorder showing similar clinical features with OFCD in affected males, and in carrier females with milder presentation. Considering the presence of bilateral 2nd-3rd toe syndactyly and septal heart defects, which is unique to OFCD, the mutation in BCOR is likely to be the major determinant for the phenotypes in this family.

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“…Both NCOR and SMRT bind to BCL6 via a conserved 17-residue BCL6 binding domain (BBD) [37]. BCOR forms a completely different type of complex than NCOR and SMRT [39]. Specifically, BCOR associates with a polycomb/ubiquitin ligase complex containing RING1, RYBP, NSPC1, RNF2, FBXL10 and Skp1 (S-phase kinase-assocated protein 1) [40].…”

Section: Biochemical Mechanisms Of Action Of Bcl6mentioning

confidence: 99%

“…Specifically, BCOR associates with a polycomb/ubiquitin ligase complex containing RING1, RYBP, NSPC1, RNF2, FBXL10 and Skp1 (S-phase kinase-assocated protein 1) [40]. The BBDs of NCOR and SMRT are identical, whereas the BCOR BBD is completely different, yet all three bind to the BCL6 BTB lateral groove in perfectly overlapping configurations [37,39]. BCL6 appears to recruit two distinct repression complexes at promoters and enhancers via its BTB domain [41].…”

Section: Biochemical Mechanisms Of Action Of Bcl6mentioning

confidence: 99%

Mechanisms of action of BCL6 during germinal center B cell development

Huang

Melnick

2015

Sci. China Life Sci.

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The transcriptional repressor B cell lymphoma 6 (BCL6) controls a large transcriptional network that is required for the formation and maintenance of germinal centers (GC). GC B cells represent the normal counterpart of most human B-cell lymphomas, which are often characterized by deregulated BCL6 expression or BCL6-mediated pathways. BCL6 suppresses gene transcription largely through recruitment of its co-repressors through its distinct repression domain. Understanding the precise biological roles of each repression domain in normal and malignant B cells is helpful for development of targeted inhibition of BCL6 functions that is emerging as the basis for design of anti-lymphoma therapies. This review focuses on recent progress in the molecular mechanisms of action of BCL6 in B cells and discusses remaining unresolved questions related to how these mechanisms are linked to normal and malignant B cell development. BCL6, germinal center, co-repressor, lymphoma Citation:Huang CX, Melnick A. Mechanisms of action of BCL6 during germinal center B cell development.

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Structure of a BCOR Corepressor Peptide in Complex with the BCL6 BTB Domain Dimer

Cited by 153 publications

References 24 publications

Drosophila BTB/POZ Domains of “ttk Group” Can Form Multimers and Selectively Interact with Each Other

Drosophila BTB/POZ Domains of “ttk Group” Can Form Multimers and Selectively Interact with Each Other

A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS

Mechanisms of action of BCL6 during germinal center B cell development

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